Hepatitis C in Pakistan: a review of available data.

Hepatitis C virus (HCV) infection is increasingly recognized as a major health care problem, and is found frequently in Pakistani settings. In this article we reviewed published and unpublished data related to the seroepidemiology of HCV infection in Pakistan. For this article, data from 132 published studies and three unpublished data sets published/ presented between the period 1992-2008 were utilized. Data of 1,183,329 individuals were gathered. Blood donors (982,481) and the general population (178,322) constituted the majority of these subjects. The frequency of HCV infection in blood donors and in the general population was 3.0 % (95% CI: 3.0- 3.1) and 4.7 (95% CI: 4.6 -4.8), respectively. The frequency among 6,148 pregnant females was 7.3% (95% CI = 6.7 – 8.0). The frequency in healthy children ranged from 0.4 to 4.1% (95% CI = 1.4 – 2.3). Pakistani HCV serofrequency figures are significantly higher (P < 0.0001) compared to those of the corresponding populations in surrounding countries like India, Nepal, Myanmar, Iran and Afghanistan.


Introduction
T he World Health Organization (WHO) has compared hepatitis C to a "viral time bomb" and estimates that about 180 million people (some 3% of the world's population) are infected with hepatitis C virus (HCV), 130 million of whom are chronic carriers at risk of developing liver cirrhosis and/or liver cancer. Three to four million persons are newly infected each year, 70% of whom will develop chronic hepatitis. HCV is responsible for 50-76% of all liver cancer cases, and two thirds of all liver transplants in the developed world (1) . World Health Statistics 2008 lists cirrhosis of the liver as the 18 th commonest cause of mortality in the world, and it is estimated that by 2030, liver cancer will become the 13 th commonest cause (2) .
The prevalence of hepatitis varies from country to country, and at times it will also vary among different regions of the same country. The epidemiological estimates by WHO show that the prevalence of hepatitis C is low (< 1%) in Australia, Canada and northern Europe, and about 1% in countries of medium endemicity, such as the USA and most of Europe. It is high (>2%) in many countries of Africa, Latin America, Central and South-East Asia. In these countries, prevalence figures between 5% and 10% are frequently reported (1) .
Collecting and comparing health data from across a country is a way to describe health problems, identify trends and help decision-makers set priorities. The global epidemiology of hepatitis C is well established. However, its epidemiology in Pakistan is ill-defined.

Hepatitis C in Pakistan
Most of the data have come from hospital-based studies, because there is a dearth of communitybased ones (3)(4)(5) . Although the National Survey of Hepatitis has concluded, its results have not yet been officially published, except for a few presentations made by researchers at official meetings. This review summarizes the available data on the epidemiology of hepatitis C since the first report of its recognition in 1992.

HCV-Related Pakistani Data
All available Pakistani data published or unpublished till the writing of this article were collected by a literature search through electronic databases like Pubmed, Pakmedinet, Yahoo and Google etc. Unpublished data from any source, if accessible, were also reviewed. Data from 132 published studies and 3 unpublished data sets were gathered and grouped in six categories, based on the type of population studied i.e. 1) general population, 2) blood donors, 3) patients with liver diseases, 4) patients with diseases other than hepatic diseases, 5) pregnant women and 6) children. Most of the data (78.5%) pertained to the years 2001-2008.
Year by year distribution of this data is given in Table 1.

General Population
Twenty-five studies  pertained to the serofrequency of hepatitis C in the general population. Details are given in Table 2. The majority of these studies (92%) were conducted during the period 2000-2008. Two studies were conducted in the nineties (6,7) . The data of 178,322 persons were included in this group. Unfortunately, there was no study from any major city of Balochistan, or from the NWFP provinces. The frequency of HCV infection ranged from 0.4% in Karachi (6) to 33.7% in Jarwar (Sindh) (28) . The mean frequency was 4.7% (95% confidence interval [CI]: 4.6 -4.8).

Blood Donors
Blood donor data constituted the largest data set. There were 27 studies and 3 unpublished data sets in this group. The total population covered in this group was 982,481 over the period 1996-2008 ( Table  3). The studies covered all provinces of Pakistan. The serofrequency of HCV ranged from 0.3% in Multan (31) to 12.5% in Islamabad (32) . The mean frequency was 3.0% (95% CI: 3.0-3.1). Only five studies (29,(32)(33)(34)(35) showed a frequency of > 5%.

Patients with Liver Diseases
Forty-one studies  dealing with the frequency of hepatitis C among patients with liver diseases were found, covering 7,765 patients over a period of 27 years from 1992 to 2008 (Table 4, and 5). Liver diseases included cirrhosis, chronic liver disease, chronic active hepatitis and hepatocellular carcinoma.

Discussion
Many researchers have tried to derive a national or regional figure for HCV serofrequency based on the available data (99)(100)(101) . In 2005, Umar M and Khaar HTB (99) , from Rawalpindi, collected data from various studies and reported a 9.8% frequency in 79,192 individuals. In 2006, Hafeez (99) , from Islamabad, collected data from 98 studies and produced an estimate of 5.3%. Raja and Janjua (101) , from Essex (UK), analyzed studies available on Medline from 1970 to 2005, and observed that the prevalence of HCV infection ranges from 0.4% in children, to 1.2% in healthy blood donors. Ali et al.  According to the "Burden of Disease Study" carried out by Hyder and Morrow in 2001, chronic liver diseases are the 5 th commonest cause of premature mortality in Pakistan and the 11 th commonest cause of disabilities (102) . Although between 75-85% of infections move on to chronic hepatitis C, the progress may be slow. Hence most people who are infected do not experience symptoms and are unaware of their infection. They are not able to benefit from available treatment that may clear them of the virus. They may also unknowingly spread the virus to others. Currently, there is no vaccine to prevent HCV infection. Effective but costly treatment is available. The high frequency and its contribution to premature mortality and disability call for massive awareness campaigns to combat the menace of this infectious disease.

Conclusions
The frequency of hepatitis C infection in Pakistan is high (4.7%), varying from 0.4% -33.7%, indicating pockets of infections. The frequency is significantly higher than in surrounding countries. The contribution of this high frequency to premature mortality and disability calls for massive awareness campaigns.